Peds Anesthesia Pharmacology Flashcards
Pharmacology differences in peds
- large Vd for water soluble meds (due to higher TBW)
- decreased Vd for fat-soluble drugs (lower amt of fat)
- altered and reduced protein binding (increases free fraction of meds)
- longer half-lives (secondary to immature hepatic/renal fxn)
- immature BBB
peds dosing
-based on per kg recommendation
50th percentile weight formula
(age x 2) + 9
less than 1 year old –> age (months)/2 + 4
volume of distribution peds
- neonates have a proportionately higher total water content 70-75% (adult is 50-60%), reduced % of fat, reduced amounts of lean muscle mass
- these differences result in a ECF volume of distribution proportionately higher than that of an adult
water soluble drugs
- increased Vd related to higher total water content
- large initial doses of water-soluble drugs are required
- potentially delayed excretion
- succ, bupi, many abx
fat soluble drugs
- decreased Vd of fat soluble lugs related to decreased fat and muscle mass
- increased DOA because there is less tissue mass into which the drug can distribute
- thiopental, fentanyl
- membrane permeability is HIGH in the newborn
- by age 2 improved BBB
protein binding of drugs peds
- reduced total serum protein concentrations
- more of the administered drug is free in the plasma to exert clinical effect
- lido and alfentanil
- reduced dosing may be needed for drugs such as barbiturates and LAs
hepatic metabolism of drugs peds
- hepatic enzymes usually convert meds from less polar state (lipid soluble) to a more polar water-soluble compound
- this ability is reduced in neonates
- the ability to metabolize a conjugate medication improves with age with both increased enzyme activity and increased delivery of drugs to the liver
renal excretion of drugs peds
- renal function less effeciant than in adults
- GFR and tubular fxn develop rapidly in first few months of life
- aminoglycosides and cephalosporins have prolonged elimination 1/2 life
inhalation agents in peds
- concentration of inhaled anesthetics in alveoli increase more rapidly with decreasing age
- more rapid inhalation induction
- excretion and recovery of inhaled anesthetics is also more rapid
- OD occurs quickly and is leading cause of serious complications (like bradycardia and hypotension)
determinants of the wash-in of inhaled anesthetics
- inspired concentration
- alveolar ventilation
- FRC
- CO
- solubility (wash in is inversely related to the blood solubility)
- alveolar to venous partial pressure gradient
inhaled anesthetics peds reasons for increased onset
- increased RR (higher minute ventilation, so faster onset)
- decreased FRC
- increased CO distribution to vessel-rich groups (straight to brain)
- these factors result in rapid RISE in alveolar anesthetic concentration that rapidly equilibrates with blood concentrations
- popular use of N2O allow for 2nd gas effect will speed induction further
other explanations for differences in peds for inhalation
- cerebral maturation
- age-related differences in blood-gas partition coefficients
- state of hydration/dehydration
- type of anesthesia circuit
- vaporizer design
inhaled anesthetics peds differences from adults
- faster induction + immature cardiac development = increased risk OD
- blood pressure very sensitive to volatiles
- MAC changes with age
- removal of inhaled agents also rapid
- all of them potentiate actions of NDMRs
Why is BP very sensitive to volatiles in kids?
- lack of compensatory mechanisms
- immature myocardium
- reduced calcium stores
how does MAC change with age?
- infants have higher MAC than noted in older children or adults
- peaks around 3 months of age
Sevoflurane MAC neonates
3.2
Sevoflurane MAC infants
3.2
Sevoflurane MAC small children
2.5
Isoflurane MAC neonates
1.6
Isoflurane MAC infants
1.8
Isoflurane MAC small children
1.4
Desflurane MAC neonates
9.2
Desflurane MAC infants
10
Desflurane MAC small children
8.2
stage I of anesthesia
- stage of analgesia or disorientation
- from beginning of induction of GA to loss of consciousness
stage II of anesthesia
- stage of excitement or delirium
- from loss of consciousness to onset of automatic breathing
- eyelash reflex disappear but other reflexes remain intact and coughing, vomiting, and struggling may occur
- respiration can be irregular with breath holding
stage III of anesthesia
- stage of surgical anesthesia
- from onset of automatic respiration to respiratory paralysis
- divided into four planes
stage III plane I of anesthesia
- from onset of automatic respiration to cessation of eyeball movements
- eyelid reflex lost, swallowing reflex disappears, marked eyeball movement may occur
- conjunctival reflex lost at the bottom of this plane
stage III plane II of anesthesia
- from cessation of eyeball movements to beginning of paralysis of intercostal muscles
- laryngeal reflex lost although inflammation of upper respiratory tract increases reflex irritability
- corneal reflex disappears
stage III plane III of anesthesia
- from beginning to completion of intercostal muscle paralysis
- diaphragmatic respiration persists but there is progressive intercostal parlyasis
- pupils dilated
- light reflex abolished
- laryngeal reflex can still be initiated by painful stimuli
- desired plane for surgery when muscle relaxants were not used
stage III plane IV of anesthesia
-from complete intercostal paralysis to diaphragmatic paralysis
stage IV of anesthesia
-anesthetic overdose causing medullary paralysis and vasomotor collapse
Nitrous Oxide Peds
- commonly used in peds to facilitate inhalation induction
- enhances rate of uptake of inhaled anesthetic
- also provides analgesia and amnesia during maintenance
- oderless, insoluble
- MAC 104%
- contraindicated in pneumo, necrotizing enterocolitis, bowel obstruction, etc.
- N2O 70% doubles size of a pneumo in 12 minutes
- may contribute to PONV
2nd gas effect
- daltons law of partial pressure - sevo, oxygen, nitrous each at 33%
- N2O diffuses faster into the blood than the other two
- now alveoli has 50% of each sevo and oxygen
- creates diffusion gradient for sevoflurane
sevoflurane
- agent of choice for inhalation induction
- blood gas 0.68 or 0.65
- least irritating to airway of inhaled anesthetics
- dose related depression in RR and TV
- common to begin with N2O then add sevo
- single vital capacity breath induction
- high temperature gas mixtures, low fresh gas flow rates <2L/min, use of CO2 absorbers containing barium hydroxide or soda lime can increase the production of compound A
isoflurane
- blood gas coefficient 1.43 (1.46)
- slower and more pungent (major disadvantage)
- appropriate to use in peds, especially after inhalation induction
- potentiates NDMR to a greater extent than sevo or des
- least costly inhalation agent
desflurane
- smallest blood gas coefficient 0.42
- most pungent causes airway irritation (50% incidence of laryngospasm if used during induction)
- better use is maintenance
- use with LMA is controversial
- emergence rapid
propofol
- highly lipophilic
- rapid distribution from plasma to peripheral tissues
- requires larger induction doses related to increased Vd
- elimination 1/2 shorter
- higher rate of plasma clearance
- risk for infection (discard after 6 hours of opening)
prop dose in peds
- IV induction 1-3 mg/kg
- TIVA infusion 25-200 mcg/kg/min
- intraoperative nerve monitoring TIVA < 120-130 mcg/kg/min or else it may interfere with SSEP and MEP
propofol MOA
-presumed to exert its sedative-hyponotic effects through an interaction with GABA, the principle inhibitory NT in the CNS
propofol effects on CV system
- produces decrease in systemic vascular resistance and SBP
- may produce profound hypotension in critically ill infants
propofol effects on ventilation
-produces dose-dependent depression of ventilation
ketamine
- widely used in peds
- dissociation of cerebral cortex
- analgesic and amnestic - commonly used in burns/dressing changes
- multiple routes and uses
- preserves spontaneous respirations an aids to maintain and patent airway, however apnea and laryngospasm may still occur
ketamine dosing peds
- oral = 6-10 mg/kg
- IM sedation = 2-5 mg/kg
- IV induction = 1-2 mg/kg
- IV pain = 0.5 mg/kg bolus; 4 mcg/kg/min infusion
- IM induction = 5-10 mg/kg
ketamine side effects
- secretions
- vomiting
- hallucinations
ketamine MOA
- produces dissociative anesthesia
- may resemble cataleptic state
- patient’s eyes may remain open with slow nystagmus (warn parents if in OR)
ketamine effects of CV system
- effects resemble SNS stimulation
- increased BP
- increased pulmonary pressures
- increased HR
- increased CO
ketamine efefcts of ventilation
- does not produce significant respiratory depression unless given by rapid IV dose
- does produce bronchodilation and use useful in asthmatic patients
etomidate
- not wisely used in children
- pain on injection, myoclonus, anaphylactoid reactions, and suppression of adrenal function
- hyponotic steroid based induction agent
etomidate dose
0.2-0.3 mg/kg
etomidate main advantage
CV stability in hypovolemic patients
etomidate main disadvantage
adrenocortical suppression not well tolerated in critically ill children
etomidate MOA
presumed to produce CNS depression via an ability to enhance the inhibitory NT GABA
etomidate effects on CV system
produces minimal changes in HR and CO
etomidate effects on ventilation
produces dose-dependent depression of ventilation
opioids in peds
- more potent effects in peds
- considered to be a result of an immature BBB
- increased sensitivity of the respiratory centers
morphine in peds
- 0.025 mg/kg IV
- histamine release
- hepatic conjugation reduced
- renal clearance decreased
- used quite a bit in peds
fentanyl in peds
- increased DOA in high doses r/t decreased fat/muscle
- synthetic opioid agonist
- acts at stereospecific opioid receptors in CNS
- used to produce analgesia, and to blunt the circulatory response to direct laryngoscopy
- OOA almost immediate when given IV
- max analgesic and resp depressant effect may not be noted for several minutes
- DOA 30-60 min
fentanyl dosing
-IV 0.25-1 mcg/kg
-IV infusion 0.5-2 mcg/kg/hr
induction usually 1 mcg/kg
hydromorphone
- semi synthetic opioid agonist
- derivative of morphine but 5x more potent
- commonly administered IV and epidural
- OOA 5 min
- DOA 2-3 hours
- patients with compromised renal function at risk of metabolite accumulation and associated neuroexcitation symptoms (tremor, agitation, cognitive dysfunction)
naloxone
- antagonizes opioids
- reduces respiratory depression, N/V, pruritis, urinary retention
- always titrate slowly
- rapid onset
- elimination half-life 1.5-3 hours
- OD can lead to HTN, cardiac arrythmias, and pulmonary edema
naloxone dose
-0.25-0.5 mcg/kg repeated doses until effect
max 2 mg
midazolam doses
- premedication = 0.5 mg/kg PO (onset 20 min); 0.2-0.3 mg/kg intranasal; 0.05 mg/kg IV (onset 5 min)
- PICU sedation = 0.4-2 mcg/kg/min
midazolam DOA
1-6 hours
flumazenil
- reversal for benzos
- GABA receptor competitve antagonist
- rapid onset 5-10 min
- 10 mcg/kg IV
- elim half life approximately 1 hour
clonidine
- pre-synaptic alpha agonist
- binding decreases calcium levels thus inhibiting the release of norepi
- oral premed 4mcg/kg (60-90 min onset)
- can also be used as adjunct to regional
- residual sedation postop
precedex
- 8x more specific for alpha-2-adrenergic receptor than clonidine with anxiolytic, sedative, and analgesic properties
- sedation without respiratory depression
- elimination 1/2 in kids approximately 2 hours
precedex dosing
- oral = 1 mcg/kg
- intranasal = 1 mcg/kg
- IV = 0.25-1 mcg/kg over 10-15 min
- IV infusion = 0.2-2 mcg/kg/hr
muscle relaxants in peds
-neonates have an increased sensitivity to NMBDs
-reduction in release of ACh and reduced muscle mass
fetal receptors have a greater opening time, allowing more sodium to enter the cell
-all have shorter onset due to faster circulation times
-may be difficult to monitor effects with PNS
rocuronium dosing peds
- 6 mg/kg IV
1. 2 mg/kg IV RSI
cisatricurium dosing peds
0.15 mg/kg IV
vecuronium dosing peds
0.1 mg/kg IV
glyco dosing peds
0.01 mg/kg IV
neostigmine dosing peds
0.05 mg/kg IV
sugammadex dosing peds
- 2-4 mg.kg IV
- 16 mg/kg IV for 1.2 mg/kg roc dose
succ in peds
- infants require larger dose because of increased ECF volume of distribution
- has fastest onset
- recovery time similar to that of adult
- admin with atropine 0.02 mg/kg IV/IM to prevent bradycardia due to muscarinic side effects of succ
peds at increased risk of the following with succ admin
- cardiac arrhythmias
- hyperkalemia
- rhabdo
- myoglobinuria
- masseter muscle spasm
- MH
- if cardiac arrest - treat hyperkalemia
succ dosing peds
- IM intubation <10kg 2 mg/kg; >10 kg 1-2 mg/kg
- IM 4 mg/kg
- IV 0.25-0.5 mg/kg
ketorolac
- NSAID
- 0.5 mg/kg IV
- elimination half-life is approx 4 hours
- caution in impaired renal, increased risk of bleeding, impaired bone healing
- may be reserved for children >1 year
symptoms hypoglycemia
- jitteriness
- convulsions
- apnea
acute hypoglycemia management
- 10% dextrose 1-2 mL/kg
- never administer bolus of D50% due to risk of vessel necrosis and high osmolarity
- maintenance on supplemental IV dextrose infusions
- minimize preop fasting
dilute D50%
1 mL D50% in 5 mL for 0.1 g/mL or D10%
1 mL D50% in 10 mL for 0.05 g/mL or D5%
